Detection of regional and distant metastasis remains primarily dependent on non- specific anatomical or metabolic imaging techniques that cannot provide real-time information to clinicians or surgeons who depend upon subjective criteria for detection of metastatic disease during diagnostic and therapeutic procedures. Incremental advances in fluorescent imaging technology and targeted therapeutics have provided the unique opportunity for the development of cancer-specific contrast agents for optical detection of cancer by surgeons and clinicians. We hypothesize that fluorescently labeled anti- EGFR antibody can be used to detect and guide removal of microscopic regional and distant head and neck cancer metastasis. To test this hypothesis, we propose to systemically inject fluorescently labeled monoclonal anti-EGFR antibodies into immunodeficient mice bearing HNSCC cervical metastasis or pulmonary metastasis to determine the potential clinical utility of this technique. Experiments will be directed at determination of the sensitivity and specificity o the technique and estimation of the minimum volume of tumor detected by this method. PUBLIC HEALTH RELEVANCE: We propose that optical imaging of cervical lymph nodes or pulmonary metastasis of head and neck cancer will significantly improve disease detection, favor minimally invasive surgical approaches, and improve patient outcomes. Using real time optical imaging after injection of a systemic tumor-specific contrast agent, we hypothesize that subclinical disease could be detected and removed.